The long range objective of this research program is to develop and apply intramolecular Diels-Alder reactions in the synthesis of biologically active natural products. Although the IDA reaction promises to become a widely used synthetic transformation, complete control of stereochemistry is not yet a reality. Problems still exist with respect to control of ring fusion geometry, and asymmetric induction from preexisting stereocenters is not always satisfactory. These problems will be addressed in the next four-year grant period within the context of developing stereo-controlled syntheses of three natural products: chlorothricolide, the aglycone of the antibiotic chlorothricin; kijanolide, the aglycone of an antibiotic active against an unusual range of microorganisms including Propionibacterium and Plasmodium species; and nargenicin A1, an antibiotic with significant activity against Staphylococcus strains.